Mucosal vaccination induces protection against SARS-CoV-2 in the absence of detectable neutralizing antibodies

Abstract

A candidate multigenic SARS-CoV-2 vaccine based on an MVA vector expressing both viral N and S proteins (MVA-S + N) was immunogenic, and induced T-cell responses and binding antibodies to both antigens but in the absence of detectable neutralizing antibodies. Intranasal immunization with the vaccine diminished viral loads and lung inflammation in mice after SARS-CoV-2 challenge, which correlated with the T-cell response induced by the vaccine in the lung, indicating that T-cell immunity is also likely critical for protection against SARS-CoV-2 infection in addition to neutralizing antibodies.

Development of an Intranasal Gel for the Delivery of a Broadly Acting Subunit Influenza Vaccine

“…Future studies would need to be completed to evaluate this hypothesis . Additionally this platform could be used for other vaccination applications in which a mucosal immune response is important to fight the infection, such as SARS-COV-2 …”

Immunogenicity of a vaccinia virus-based severe acute respiratory syndrome coronavirus 2 vaccine candidate

“…VACV has been used as a vaccine vector for the management of infectious diseases and cancers. Several vaccinia vector-based SARS-CoV-2 vaccine candidates have been tested using a highly attenuated VACV strain Modified Vaccinia Ankara (MVA) and exhibited protection in immunized animals (22)(23)(24)(25)(44)(45)(46)(47)(48)(49). Recombinant MVA-expressing spike protein or RBD were shown to elicit strong NAb responses, produce S-specific CD8 T cells, and protect vaccinated animals against a lethal intranasal SARS-CoV-2 challenge.…”

Highly Attenuated Poxvirus-Based Vaccines Against Emerging Viral Diseases

“…No protection after intramuscular immunization. 123 MVA-S + N Soluble S protein, non-stabilized and N protein (Wuhan strain) Mouse (C57BL/6) - Binding IgGs and IgAs and NAbs in serum and BAL. Polyfunctional CD4 and CD8 T cells in spleen and lungs (Th1-profile).…”

“…SARS-CoV-2 full-length S protein is the most common antigen expressed by the different MVA vectors, either in its unmodified native non-stabilized conformation 102 , 103 , 104 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 121 , 122 , 123 , 124 or in an optimized prefusion-stabilized conformation, 106 , 107 , 116 , 117 , 118 , 119 , 120 being the MVA vectors expressing the prefusion-stabilized S protein more immunogenic and efficacious than those expressing the non-stabilized S protein. 106 , 107 , 116 , 117 , 120 Other regions of the SARS-CoV-2 S protein have also been inserted into the MVA vector, such as the receptor binding domain (RBD), the S1 region or a soluble S ectodomain, but their immunogenicity is lower than that induced by MVA vectors expressing the full-length S protein.…”

“… 106 , 107 , 116 , 117 , 120 Other regions of the SARS-CoV-2 S protein have also been inserted into the MVA vector, such as the receptor binding domain (RBD), the S1 region or a soluble S ectodomain, but their immunogenicity is lower than that induced by MVA vectors expressing the full-length S protein. 117 , 119 , 121 Furthermore, other SARS-CoV-2 antigens, such as the N protein, have been incorporated in combination with the S protein 111 , 112 , 120 , 123 , 124 to broaden the immune response against SARS-CoV-2. Most vaccine candidates contain the sequence of the ancestral Wuhan strain, but a synthetic MVA vector expressing SARS-CoV-2 S and N antigens from variant of concern (VoC) beta has been recently reported.…”